Is AAGAB p.Phe17fs (c.50del) pathogenic?

AAGAB p.Phe17fs (c.50del) is classified Likely pathogenic in AAGAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 8.48e-05%, nfe); Associated with AAGAB-related disorder.

What condition is associated with AAGAB p.Phe17fs (c.50del)?

AAGAB p.Phe17fs (c.50del) is associated with AAGAB-related disorder (ClinVar).

How common is AAGAB p.Phe17fs (c.50del) in the general population?

AAGAB p.Phe17fs (c.50del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

AAGAB p.Phe17fs

c.50del · rs2505534485 · VCV2630130

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

AAGAB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP 0.78, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,110 alleles

Overall 6.86e-05% 1/1,457,700 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AAGAB
Protein: p.Phe17fs
Coding: c.50del
MANE Select: NM_024666
dbSNP: rs2505534485
Type: Deletion
Location: chr15:67254582 (GRCh38)
Gene constraint: LOEUF 1.156 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 3 PDB
Residue 17: a β-strand

Full AAGAB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AAGAB-related disorder

Similar variants

AAGAB p.Asp115fs Likely pathogenic ★ same condition
AAGAB p.Ile111_Leu112insTer Pathogenic ★ same condition
AAGAB p.Val62fs Likely pathogenic ★ same condition
AAGAB p.Phe17Ser Uncertain significance ★ ⚠ same residue
AAGAB p.Phe17= Benign ★ same residue
AAGAB p.Arg124Ter Pathogenic ★★ same condition
AAGAB c.451+1G>A Pathogenic ★ same condition
AAGAB c.619-2A>G Likely pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/aagab-p-phe17fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown